PROJECT SUMMARY/ABSTRACT The goal of this K23 Mentored Patient-Oriented Research Career Development Award is to provide the candidate, Dr. Jason Oliver, with the training necessary to establish a career as an independent investigator conducting translational research on tobacco use and smoking cessation. Current understanding of the mechanisms responsible for driving smoking behavior is limited and existing smoking cessation treatments are modestly effective at best. The proposed training and research project center on a novel framework for understanding smoking behavior emphasizing the imbalance between rewards attainable through cigarette smoking relative to other non-smoking environmental rewards. The study will examine the effects of nicotine withdrawal on reward imbalances among 60 cigarette smokers. An innovative strategy will be used to systematically identify personally-relevant smoking and alternative rewards in order to enhance the salience of the rewards and increase the potential for findings to inform the development of clinical interventions. A translational approach will be used to assess reward responses in parallel inside the laboratory as well as outside the lab in real-time using mobile technology. In the first aim, we will examine the effects of nicotine withdrawal on neurobiological responses to images of personally-relevant smoking and non-smoking reward stimuli taken from the smoker?s natural environment using functional neuroimaging (fMRI). In the second aim, we will examine the effects of withdrawal on the frequency with which they engage in these behaviors and the magnitude of the reward response. The third aim will examine the relationship between laboratory and real- world responses. Results will enhance our understanding of the neural mechanisms of reward imbalances and the role these mechanisms play in driving smoking behavior. As part of the broader career development of the applicant, he will receive training from a team of well-established investigators with expertise related to the above topics. Dr. Adam Leventhal will provide conceptual training in the role of alternative rewards in smoking. Dr. Scott Huettel will provide conceptual training in neuroeconomics and methodological training in functional neuroimaging. Dr. Jean Beckham will provide methodological training in the assessment of real-world smoking behavior. Dr. Robert Schnoll will provide training in the design and analysis of clinical trials for smoking cessation. Dr. Joseph McClernon will guide overall professional and contribute to training in functional neuroimaging, smoking cessation clinical trials and the development of a translational research program more broadly. Ultimately, this K23 application will provide the candidate with the training and experience necessary to function as an independent research scientist conducting both basic and applied research on smoking behavior and successfully compete for R01 funding upon completion of the award.